Ulrich Guller

Concomitant Cholecystectomy During Laparoscopic Roux-en-Y Gastric Bypass in Obese Patients Is Not Justified: A Meta-Analysis

While LRYGB has become a cornerstone in the surgical treatment of morbidly obese patients, concomitant cholecystectomy during LRYGB remains a matter of debate. The aim of this meta-analysis was to estimate the rate and morbidity of subsequent cholecystectomy after laparoscopic Roux-en-Y gastric bypass (LRYGB) in obese patients. A meta-analysis was performed analyzing the rate and morbidity of subsequent cholecystectomy in patients who underwent LRYGB without concomitant cholecystectomy. Thirteen studies met the inclusion criteria. The rate of subsequent cholecystectomy was 6.8xa0% (95 % CI, 5.0–8.7xa0%) based on 6,048 obese patients who underwent LRYGB without concomitant cholecystectomy. The rate of subsequent cholecystectomy due to biliary colic or gallbladder dyskinesia was 5.3xa0%; due to cholecystitis, 1.0xa0%; choledocholithiasis, 0.2xa0%; and biliary pancreatitis, 0.2xa0%. The mortality after subsequent cholecystectomy was 0xa0% (95 % CI, 0–0.1xa0%). The surgery-related complication rate after subsequent cholecystectomy was 1.8xa0% (95xa0% CI, 0.7–3.4xa0%) resulting in a risk of 0.1xa0% (95xa0% CI, 0.03–0.3xa0%) to suffer from a cholecystectomy-related complication in patients undergoing LRYGB without concomitant cholecystectomy. A prophylactic concomitant cholecystectomy during LRYGB should be avoided in patients without cholelithiasis and exclusively be performed in patients with symptomatic biliary disease.

Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival

BackgroundLymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell depositsu2009≤u20090.2xa0mm) in loco-regional LN of stage I & II colon cancer patients.MethodsSeventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses.ResultsMedian follow-up was 4.6xa0years. ITC were detected in locoregional lymph nodes of 23 patients (31.1xa0%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratiou2009=u20094.73, pu2009=u20090.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratiou2009=u20093.50, pu2009=u20090.043).ConclusionsThis studyxa0provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.

Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona

BACKGROUND AND SCOPEnIn the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use.nnnMETHODOLOGYnOpinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine.nnnRESULTSnPreselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made.nnnCONCLUSIONnThe current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice.

Bone Marrow Micrometastases Do Not Impact Disease-Free and Overall Survival in Early Stage Sentinel Lymph Node–Negative Breast Cancer Patients

BackgroundThe presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)–negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients.MethodsWe analyzed 410 patients with early stage breast cancer (pT1 and pT2xa0≤xa03xa0cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19.ResultsNegative SLN were found in 67.6xa0% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8xa0% (210 of 277) and positive in 24.2xa0% (67 of 277) patients. Median follow-up was 61 (range 11–96) months. Five-year disease-free survival was 93.6xa0% (95xa0% confidence interval [CI] 89.1–96.0) in BMM-negative and 92.2xa0% (95xa0% CI 82.5–96.2) in BMM-positive patients (pxa0=xa00.50). Five-year overall survival was 92.7xa0% (95xa0% CI 87.9–95.8) for the BMM-negative and 92.5xa0% (95xa0% CI 83.4–96.2) for the BMM-positive group (pxa0=xa00.85).ConclusionsThis is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Predictive Value of CEA for Survival in Stage I Rectal Cancer: a Population-Based Propensity Score-Matched Analysis

BackgroundThe aim of the study was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall- and cancer-specific survival in stage I rectal cancer.MethodsStage I rectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 2004 and 2011. The impact of an elevated preoperative CEA level (C1-stage) compared with a normal CEA level (C0-stage) on overall and cancer-specific survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods.ResultsOverall, 1932 stage I rectal cancer patients were included, of which 328 (17xa0%) patients had C1-stage. The 5-year overall and cancer-specific survival for patients with C0-stage were 85.7xa0% (95xa0% CI 83.2–88.2xa0%) and 94.7xa0% (95xa0% CI 93.1–96.3xa0%), versus 76.8xa0% (95xa0% CI 70.9–83.1xa0%) and 88.1xa0% (95xa0% CI 83.3–93.2xa0%) for patients with C1-stage (Pu2009<u20090.001 and Pu2009=u20090.001). The negative impact of C1-stage on overall and cancer-specific survival was confirmed by risk-adjusted Cox proportional hazard regression analysis (hazard ratio [HR]u2009=u20091.57, 95xa0% CIu2009=u20091.15–2.16, Pu2009=u20090.007 and 2.04, 95xa0% CIu2009=u20091.25–3.33, Pu2009=u20090.006), and after propensity score matching (overall survival [OS]: HRu2009=u20091.46, 95xa0% CIu2009=u20091.02–2.08, Pu2009=u20090.044 and cancer-specific survival [CSS]: HRu2009=u20093.28, 95xa0% CIu2009=u20091.78–6.03, Pu2009<u20090.001). ConclusionThis is the first population-based investigation of a large cohort of exclusively stage I rectal cancer patients providing compelling evidence that elevated preoperative CEA level is a strong predictor of worse overall and cancer-specific survival.

Intranodal Mapping Using Carbon Dye Results in More Accurate Lymph Node Staging in Colon Cancer Patients

IntroductionSmall nodal tumor infiltrates (SNTI)—defined as isolated tumor cells and micrometastases—are associated with worse disease-free and overall survival in stage I and II colon cancer patients. Their detection, however, remains challenging. The objective of the present study was to evaluate whether there is a correlation between the location of SNTI and phagocytosed carbon dye particles in sentinel lymph nodes (SLN) of colon cancer patients.Materials and MethodsIsosulfan blue and carbon dye were injected intraoperatively near the tumor to mark the SLN. Serial sections of SLN were stained with hematoxylin–eosin and immunohistochemistry. Intranodal distribution of phagocytosed carbon particles was compared to the presence of SNTI.ResultsOf a cohort of 159 patients, 24 patients had SNTI in their lymph nodes (LN). SNTI were found in a total of 116 LN of which 66 were SLN and 50 were non-SLN. In 59, these 116 LN with SNTI phagocytosed carbon dye were found (50.9xa0%). Phagocytosed carbon dye was identified significantly more often in SLN (49 of 66 SNTI positive SLN) compared to 10 of 50 SNTI positive non-SLN (pxa0<xa00.001). In 52 out of 59 LN (88.1xa0%), phagocytosed carbon dye was in close proximity to SNTI.ConclusionsIn the majority of patients, SNTI are located in the same SLN compartment as phagocytosed carbon dye particles. Our investigation provides evidence that the use of carbon dye facilitates SNTI detection and improves LN staging in colon cancer. Therefore, the concept of intranodal mapping—which has been previously described for melanoma—can be extended to colon cancer patients.

The prognostic value of signet ring cell histology in stage I/II colon cancer—a population-based, propensity score-matched analysis

BackgroundPrevious research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer.MethodsStage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.ResultsEighty-eight thousand nine hundred fifty-eight stage I–II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, pu2009<u20090.001; CSS, pu2009<u20090.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82–1.12%) pu2009=u20090.616; CSS: HR, 1.01 (95% CI, 0.79–1.28%) pu2009=u20090.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82–1.14%) pu2009=u20090.669 and CSS: HR: 1.09 (95% CI: 0.84–1.40%) pu2009=u20090.529), a survival disadvantage was found for signet ring cell histology.ConclusionThis is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona, June 2018

Patients with hereditary gastrointestinal (GI) cancers represent a substantial fraction of the overall affected population. Although awareness for hereditary GI cancer syndromes is on the rise, identification of patients and measures of surveillance are often unclear in everyday clinical routine. Therefore, the European Society of Digestive Oncology expert discussion 2018 at the World Congress on Gastrointestinal Cancer focussed on screening and surveillance of hereditary colorectal, gastric and pancreatic cancers. An international panel of experts and opinion leaders developed the here presented recommendations based on published evidence and on profound clinical expertise to facilitate clinical routine in identification and caretaking of patients with familial GI cancers.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes

BackgroundThe lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN.MethodsOne hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3xa0months.ResultsFifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8–54). DFS and OS were significantly shorter in pN2 vs pN1 patients (pu2009<u20090.001, and pu2009=u20090.001, respectively), and in LNR high vs low patients (pu2009=u20090.032, and pu2009=u20090.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (pu2009<u20090.001), and 6.8 (pu2009<u20090.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (pu2009=0.041), and 4.5 (pu2009=u20090.054).ConclusionsLNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

Blue dye injection does not induce dissemination of epithelial cells during SLN procedure in colon cancer patients

IntroductionThe sentinel lymph node (SLN) procedure for colon cancer patients has been increasingly performed over the past decade and has shown advantages regarding lymph node staging. However, there are concerns that the manipulation of the colon, particularly the blue dye injection, results in isolated tumor cell dissemination to lymph nodes. Therefore, the objective of the present study was to evaluate whether the blue dye injection during the SLN procedure for colon cancer induces epithelial cell dissemination to the regional lymph nodes using a fake SLN procedure as a model.MethodsOne hundred seventy-four colon cancer patients underwent open oncologic colon resection and SLN procedure according to a standardized protocol. For the fake SLN procedure, blue dye was injected ex vivo, into the subserosa of a nontumor-bearing segment of the resected colon in 37 unselected patients. Three levels of each SLN were stained with H&E and with the pancytokeratin marker AE1/AE3 and were analyzed for the presence of cytokeratin positive cells.ResultsIdentification of fake SLN was successful in 32 of the 37 patients (86xa0%). Seventy fake SLN were histologically confirmed. The median number of fake SLN was 2 per patient (range 1–8). None of the fake SLN showed any disseminated epithelial cells.ConclusionsThe present prospective study provides compelling evidence that blue dye injection during sentinel lymph node procedure for colon cancer does not induce epithelial cell dissemination to the sentinel lymph nodes. Therefore, isolated tumor cells in sentinel lymph nodes result from a true metastatic process.